Project Summary Since the eradication of poliomyelitis, Guillain-Barr syndrome (GBS) has become a major health burden in low-income countries. The prognosis of GBS has not improved over the last two decades. Our group previously showed that the incidence, disease severity and mortality of GBS are higher in Bangladesh compared to the developed world. The preferred and most effective treatment for severe GBS is intravenous immunoglobulin (IVIg), yet some patients respond poorly to this recommended therapy. Little is known about the factors that influence disease pathogenesis and recovery in patients receiving IVIg therapy in low-income countries. Our long-term goal is to identify key determinants that predict IVIg treatment response in patients with GBS from low-income countries. The main hypothesis of the proposed project is that biological markers, nutritional factors or microbial strain differences may potentially influence the response of IVIg or clinical course and outcome of patients with GBS in low-income countries. Our objective is to identify key determinants to measure IVIg treatment responsiveness in patients with GBS in Bangladesh. Our specific aims will test the following hypotheses: Specific aim #1: We will identify whether biological markers serve as predictive factors to determine IVIg treatment response or whether nutritional status affects IVIg treatment response, the clinical course and GBS disease outcome in a low-income country. Specific aim #2: We will use high- throughput sequencing to generate and compare the whole genome sequences of Campylobacter jejuni strains isolated from IVIg-treated and non-treated patients with GBS, in order to identify the key genetic determinants responsible for disease pathogenesis and outcomes of IVIg treatment in low-income countries. The research proposed in this career development application is built upon ongoing, long-standing collaborative efforts between the icddr,b (Bangladesh), Erasmus University Medical Centre (the Netherlands), the University of Texas (USA), Washington State University (USA) and the National Institute of Neurosciences & Hospital (Bangladesh). The goal of this Career Development Program is to strengthen the skills necessary to become an independent researcher/investigator in host-pathogen interaction and advanced genomics research.